Allergic sensitivity to plant proteins in the sap of the rubber tree has become a major occupational hazard of health care workers and some patients with frequent latex rubber exposures. Between 2.2 and 10.7% of health care workers and 1-2% of laboratory personnel are at risk for systemic reactions to rubber products, mainly latex gloves. Systemic latex reactions are predominantly of inhalant origin because cornstarch particles used to lubricate surgical gloves serve as a respirable carrier for the protein allergens. Since complete avoidance is difficult in most medical environments, latex allergy can necessitate involuntary career changes with substantial economic and emotional consequences. Using a latex allergen extract now being standardized for diagnostic purposes, this project proposes to develop further a natural exposure model of respiratory latex allergy and to use this model in clinical studies to demonstrate the safety and efficacy of immunotherapy for IgE-dependent latex allergy. The specific aims are: (1) to validate a prototype hooded environmental chamber technique as a provocational challenge model of respiratory allergy to natural rubber latex; (2) to conduct a Phase 1 clinical trial of immunotherapy with a candidate extract of non-ammoniated latex; and (3) to determine in a randomized, placebo-control clinical trial the safety and clinical efficacy of immunotherapy with a candidate vaccine in patients with disabling occupational allergy to latex proteins. Subjects will be health professionals with clinically significant respiratory or anaphylactic reactions to latex and documented failure of attempts at avoidance. The primary endpoint will be sensitivity to latex as determined by the hooded chamber graded exposure technique. Secondary endpoints for the clinical trial will include immunologic changes (IgG and IgE fluxes), skin test sensitivity, adverse reaction rates, and where possible assessments of work-related symptoms. The long-range objective of this research plan is to develop a useful therapeutic alternative for latex-sensitive health care workers and selected patients who have failed avoidance. Potential benefits include a reduction in professional disability, prevention of chronic disease, expanded occupational choices, and increased work productivity for those affected.